MiR-429 reverses epithelial-mesenchymal transition by restoring E-cadherin expression in bladder cancer

Epithelial-mesenchymal transition (EMT) accompanying loss of E-cadherin is important for invasiveness and metastasis of bladder cancer. MicroRNAs (miRs) had been associated with cancer progression and differentiation in several cancers.

Our goal is to find out the specific miR which modulates EMT in bladder cancer. Real-time quantitative polymerase chain reaction was used to measure the miRs expression in urothelial cell carcinoma (UCC) cell lines. MiR or siRNA mimics was used to regulate miR and mRNA level respectively. Migration and scratch assays were used to determine the migratory ability. Zymography assay was used to confirm the metalloproteinase activity. Western blotting was used to elucidate the mechanism which regulated by specific miR. MiR-429 was highly expressed in low grade UCC cell lines. Exogenous mimic of miR-429 treatment dramatically inhibited the migratory ability of T24 cells. MiR-429 downstream target ZEB1 was decreased, E-cadherin was restored, and β-catenin was contrarily decreased by exogenous mimic of miR-429 treatment in T24 cells. Cell invasive ability was also inhibited by exogenous mimic of miR-429 treatment through inactivating the MMP-2 activity in T24 cells. E-cadherin protein expression level was inhibited by E-cadherin siRNA accompanied with increasing cell migratory ability when compared with control group in low grade TSGH8301 cells. MiR-429 decreased the cell migratory and invasive abilities through reducing ZEB1 and β-catenin, restoring the E-cadherin expression and inactivation of MMP-2 of UCC cells. MiR-429 might be used as a progression marker of bladder cancer.

Oncotarget. 2016 Apr 02 [Epub ahead of print]

Chia-Lun Wu, Jar-Yi Ho, Sheng-Chieh Chou, Dah-Shyong Yu

Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan., Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Division of Urology, Department of Surgery, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan., Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.